Fecal incontinence is a common disorder in men and women, though more prevalent in women. The mechanisms causing anal incontinence usually involve reduced resting tone of the external and internal anal sphincters, and damage in the levator ani muscles, especially, the puborectalis muscle.
Conventional treatments of fecal incontinence include pelvic floor rehabilitation by exercises or surgical interventions and drug therapy. Biofeedback training is one of the treatments involving muscle strengthening exercises to improve anal canal resting and squeeze pressure, and to improve the symmetry of anal canal function.
Drug therapy is mostly directed to improve stool consistency and includes the use of morphine and loperamide among others. Drug therapy also includes administration of codeine phosphate to reduce gut motility (peristalsis), or laxatives to soften stools and relieve constipation. Therapy with sodium valproate was found to be useful in the treatment of minor incontinence after ileoanal anastomosis (Kusunoki et al., Surgery, 1990, 107:311-315). It was also shown that in vitro contractile response of the internal anal sphincter to noradrenaline is decreased in incontinence (e.g. Speakman et al., Digestive Diseases and Sciences, 1993, 38(11):1961-1969). Therapy with Solesta™, a viscous biocompatible bulking agent, was shown to be superior to sham treatment, resulting in 50% reduction of incontinence episodes.
Yet, the most common form of treatment is surgical repair, such as, the creation of a neo-sphincter which involves grafting on muscle from other parts of the anus, or a colostomy. However, success rates of surgeries, such as external anal sphincteroplasty, are around 50% or less.
Recent drug therapies directed to increase the anal resting pressure of a patient having a reduced anal resting pressure are disclosed in U.S. Pat. Nos. 6,635,678 and 7,781,444. Therapy according to these publications involves topical administration in and/or around the anal canal of a patient a composition comprising at least 5% w/w of an α-adrenergic agonist, particularly, noradrenalin, methoxamine and phenylephrine. However, according to these publications no significant increase in the maximum resting pressure was observed for phenylephrine concentrations below 10%, where the recommended concentrations are of 10-30% phenylephrine.
Oxymetazoline is an α-adrenergic agonist commercially known for long as a topical decongestant in the form of nasal sprays, such as, Afrin™ (e.g. U.S. Pat. No. 6,824,762). Topical application of oxymetazoline was also suggested for treating sympathetically maintained pain in peripheral tissues (e.g. RE 41,998), for reducing or eliminating pain associated with a syringe, needle stick, or lancet stick as a vasoconstrictor combined with local anesthetic (e.g. U.S. Pat. No. 7,883,488) and for ameliorating telangiectasias (U.S. Pat. No. 7,838,563) among other uses.
To date, no particularly efficient drug therapy for treating ano-rectal disorders, such as, fecal incontinence is known.